The non-medical use of prescription stimulants and use of methamphetamine continues to be prevalent among young adults and is an enormous public health problem. As many as 1 in 10 American young adults aged 16?25 years reported misuse of stimulants in their lifetime and 1 out of 7 of these individuals develop stimulant dependence. This proposal aims to continue ongoing work to identify which brain processing differences predict transition from occasional stimulant use to dependence. Our main findings have been: (1) Attenuated insula response during risk taking, which may be related to reduced interoceptive signaling;(2) Increased prefrontal activation in the presence of equal inhibitory performance, which implies inefficient inhibitory processing. (3) Reduced modulation of striatum to different levels of errors in decision situations. However, we have also found significant heterogeneity among stimulant users depending on the context in which stimulant use takes place that point towards opposite processing differences in ?partiers? versus ?studiers?. The fundamental hypothesis proposed here is that stimulant users at highest risk for transition to dependence exhibit an increased propensity to take risks because of attenuated processing in risk-related brain structures. We propose that this is due to the fact that the insular cortex of these individuals does not signal as effectively potentially aversive outcomes (in terms of internal body states). The two specific aims are: (1) To determine neural processing differences in cohort 1 across individuals who develop dependence and those who do not. This the longitudinal component of the first cohort study, which will not include an fMRI experiment for a subset of n=60 cohort 1 individuals. (2) To investigate a new prospective cohort 2 of 60?studiers? and 60 ?partiers? focused on altered decision-making and interoceptive processing. This is both a cross-sectional and a 3-y follow-up study to examine the hypothesis that ?partiers? but not ?studiers? are at a high risk of transitioning to dependence. This competitive renewal seeks to address two practical questions: (1) ?can neuroimaging be used as a predictive marker?? and (2) ?is there dysfunction of the interoceptive system which could be a target for intervention, e.g. using real-time fMRI??